Is CHRNE p.Ser445fs (c.1332del) pathogenic?

CHRNE p.Ser445fs (c.1332del) is classified Pathogenic in CHRNE (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-11). Absent from gnomAD; Associated with congenital myasthenic syndrome 4A.

What condition is associated with CHRNE p.Ser445fs (c.1332del)?

CHRNE p.Ser445fs (c.1332del) is associated with congenital myasthenic syndrome 4A (ClinVar).

How common is CHRNE p.Ser445fs (c.1332del) in the general population?

CHRNE p.Ser445fs (c.1332del) is absent from gnomAD (gnomAD).

CHRNE p.Ser445fs

c.1332del · rs2509299907 · VCV2033252

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

congenital myasthenic syndrome 4A

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (12 of 12) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.7	GERP 0.74, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CHRNE
Protein: p.Ser445fs
Coding: c.1332del
MANE Select: NM_000080
dbSNP: rs2509299907
Type: Deletion
Location: chr17:4898886 (GRCh38)
Gene constraint: LOEUF 1.298 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 25 PDB
Residue 445: an α-helix

Full CHRNE gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital myasthenic syndrome 4A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CHRNE p.Ser445= Likely benign ★ same residue
CHRNE c.1216_1219+19del Pathogenic/Likely pathogenic ★★ same condition
CHRNE c.1220-6_1227del Likely pathogenic ★★ same condition
CHRNE c.1319_1326+15del Pathogenic/Likely pathogenic ★★ same condition
CHRNE p.Ala365fs Pathogenic/Likely pathogenic ★★ same condition
CHRNE p.Ala461fs Pathogenic/Likely pathogenic ★★ same condition
CHRNE p.Ala462fs Pathogenic/Likely pathogenic ★★ same condition
CHRNE p.Arg364fs Pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/chrne-p-ser445fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown